在癌症中，KRAS的致癌突变是最常见的。经典模型表明，失去上皮特性和获得间充质特征与癌症的侵袭性和抗药性有关。然而，这些表型与突变KRAS生物学之间的机制联系仍然有待建立。我们在这里确定STAT3作为TGF-beta诱导的上皮-间充质转化的遗传修饰因子。胰腺癌细胞的基因表达谱鉴定出由STAT3和致癌KRAS共同调控的200多个基因。STAT3响应性程序的功能分类揭示了其在肿瘤维持和上皮稳态中的主要作用。STAT3激活的细胞状态的特征可以投影到人类KRAS突变肿瘤上，暗示其忠实地反映了人类疾病的特征。这些观察结果对治疗干预和肿瘤侵袭性具有重要意义。鉴定肿瘤的分子和遗传特征对于理解疾病的进展和侵袭性至关重要。KRAS突变是人类癌症中最常见的致癌驱动因子。在这项研究中，我们证明了广泛表达的转录因子STAT3是TGF-beta诱导的EMT和致癌KRAS依赖性的遗传修饰因子。无论是体外还是体内研究均表明，STAT3响应性程序是致癌KRAS结果的固有部分。

Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. However, the mechanistic link between these phenotypes and mutant KRAS biology remains to be established. Here we identify STAT3 as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition. Gene expression profiling of pancreatic cancer cells identifies more than 200 genes commonly regulated by STAT3 and oncogenic KRAS. Functional classification of STAT3 responsive program reveals its major role in tumor maintenance and epithelial homeostasis. The signatures of STAT3-activated cell states can be projected onto human KRAS mutant tumors, suggesting that they faithfully reflect characteristics of human disease. These observations have implications for therapeutic intervention and tumor aggressiveness.The identification of the molecular and genetic characteristics of tumors is essential for understanding disease progression and aggressiveness. KRAS mutations are the most frequent oncogenic drivers in human cancer. In this study we demonstrate that the ubiquitously expressed transcription factor STAT3 is a genetic modifier of TGF-beta-induced EMT, and thereby oncogenic KRAS dependency. Both in vitro and in vivo studies demonstrate that STAT3 responsive program is an inherent part of oncogenic KRAS outcome.